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The role of memory in cellular decision-making and fitness

  • Full or part time
    Prof P Swain
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Cells live in fluctuating environments, but we know little about how they respond to dynamic changes. Do cells remember and use their memory to alter their behaviour? Are current events used to predict and prepare for future events? Are memories passed on to new daughter cells or kept by the mother?
Using single-cell microscopy and microfluidic technology, you will investigate cellular responses and memory in budding yeast. We have developed a microfluidic device, called ALCATRAS, which uses micron-sized "jails" to trap an initial population of cells. All daughter cells of the trapped cells are eventually washed away by the flow of medium through the device, and we can therefore typically monitor individual cells for around 20 divisions, and often to senescence. By changing pressure on the two inflow channels, we can alter the extracellular media every few seconds and move cells, for example, in to and out of stress.

You will study the response of single cells to repetitive occurrence of stress such as exposure to low levels of nutrients. Using fluorescent proteins, you will follow new gene expression and the intracellular movement of transcription factors. You will measure cell fitness using deep-learning software that automatically counts the number of divisions each cell undergoes from the microscopy images. By correlating the cellular response with fitness, you will be able to classify cellular responses as successful or unsuccessful. Mutations and mathematical modeling will be used to explore mechanisms.
The aim is to understand the advantages and biochemistry of memory. Initially, you will study changes in carbon sources and later changes in nitrogen sources, an under explored area despite control by the conserved TOR kinase.

swainlab.bio.ed.ac.uk



Funding Notes

The “Visit Website” button on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.

If you would like us to consider you for one of our scholarships you must apply by 5 January 2020 at the latest.

References

Granados AA, Pietsch JMJ, Cepeda-Humerez SA, Farquhar IL, Tkačik G, Swain PS. Distributed and dynamic intracellular organization of extracellular information. Proc Natl Acad Sci USA. 2018; 115: 6088-6093

Mitchell A, Lim W. Cellular perception and misperception: Internal models for decision-making shaped by evolutionary experience. Bioessays. 2016; 38: 845-9

Crane MM, Clark IB, Bakker E, Smith S, Swain PS. A microfluidic system for studying ageing and dynamic single-cell responses in budding yeast. PLoS One. 2014;9:e100042

How good is research at University of Edinburgh in Biological Sciences?

FTE Category A staff submitted: 109.70

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